Ibrutinib, chemically 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one of formula (I),

is a pharmaceutically active compound. It is used for the treatment of chronic lymphocytic leukaemia (CLL) in previously untreated patients and in patients who have received at least one previous treatment. It is also used for the treatment of mantle cell lymphoma (MCL) in patients whose disease does not respond to or has come back after previous treatment and to treat Waldenström's macroglobulinaemia (WM), also known as lymphoplasmacytic lymphoma, in patients who have had previous treatment or who cannot have chemo immunotherapy.
Ibrutinib is marketed by Janssen/Pharmacyclics under the brand name Imbruvica® and is disclosed in WO2008039218. Imbruvica® was initially only supplied as hard capsule in one strength: 140 mg. Patients take either 3 or 4 capsules once daily, depending on the disease to be treated. Recently, the FDA approved a new tablet formulation of Imbruvica®. The tablet is available in the strengths 140, 280, 420 and 560 mg and thus reduces pill burden for patients.
Several crystalline forms of ibrutinib are described in literature. WO2013184572 discloses crystalline forms A, B and C and solvated forms D (methyl isobutyl ketone solvate), E (toluene solvate) and F (methanol solvate). The marketed product Imbruvica®, both capsule and tablet formulation, contains crystalline ibrutinib form A. Other forms of ibrutinib are disclosed in CN103923084, WO2015081180, WO2015145415, WO2016025720, WO2016079216, CN105294696, CN105646484, CN105646499, CN105646498, WO2016160598, WO2016139588, WO2017029586, CN106117214, WO2017085628, CN107286163, EP3243824 and WO2018000250. Some of the described forms do contain unwanted solvents. Moreover, it was experienced in our laboratory that some of these forms are rather unstable.
Ibrutinib is a BCS class II compound, exhibiting low solubility and high permeability.
Both capsule and tablet composition of Imbruvica® contain a considerable amount of the anionic surfactant sodium lauryl sulphate (SLS). It is known that this compound may give rise to irritation of the gastrointestinal tract.
It would be desirable to have a tablet composition comprising ibrutinib that exhibits adequate dissolution and is free of surfactant. The composition should be stable, suitable for production on commercial scale and bioequivalent to Imbruvica®.